Individualized pazopanib dosing

Purpose: Pazopanib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Retrospective analyses have shown that an increased median PFS and tumor shrinkage appears in patients with higher plasma trough levels (C_min). Therefore, patients with low C_min might benefit from pharmacokinetically-guided individualized dosing. Experimental Design: We conducted a prospective multicenter trial in 30 patients with advanced solid tumors. Pazopanib C_min was measured weekly by LC-MS/MS. At week 3, 5 and 7 the pazopanib dose was increased if the measured C_min was <20 mg/L and toxicity was < grade 3. Results: In total, 17 patients had at least one C_min <20 mg/L at week 3, 5 and 7. Of these, 10 were successfully treated with a pharmacokinetically-guided dose escalation, leading to daily dosages ranging from 1000 to 1800 mg daily. C_min in these patients increased significantly from 13.2 (38.0%) mg/L (mean (CV%)) to 22.9 mg/L (44.9%). Thirteen patients had all C_min levels {greater than or equal to}20 mg/L. Of these, nine patients with a high C_min of 51.3 mg/L (45.1%) experienced {greater than or equal to} grade 3 toxicity and subsequently required a dose reduction to 600 or 400 mg daily, yet in these patients C_min remained above the threshold at 28.2 mg/L (25.3%). Conclusions: A pharmacokinetically-guided individualized dosing algorithm was successfully applied and evaluated. The dosing algorithm led to patients being treated at dosages ranging from 400 to 1800 mg daily. Further studies are needed to show a benefit of individualized dosing on clinical outcomes such as progression free survival.

from Cancer via ola Kala on Inoreader http://ift.tt/2agnxvR
via IFTTT